Computational and structural imaging

Overview

Our research investigates the mechanisms underlying
regulation of blood
vessel formation and function of the mature cardiovascular system by
Vascular
Endothelial Growth Factor (VEGF) and other growth factors. A major focus
of
this work is to identify the signalling pathways and receptors involved
in
these biological functions of VEGF, communication between them and how
they
integrate into physiologically relevant networks. We are pursuing these
aims
through in vivo analysis in disease and genetic models, combined with
imaging
and biochemical studies in cell culture. Another important aspect of our
work
is the development of new therapeutic approaches designed either to
promote or
to inhibit VEGF functions dependent on the disease context. Research in
our
centre is supported by major programme grant funding from the British
Heart
Foundation, and additional funding from the European Commission (EC),
and Biotechnology and Biological Sciences Research Council (BBSRC).

Key research activities

In congenital heart disease, predicting how
patients will respond to treatments such as surgery, catheter interventions,
and pharmacology, as well as determining which treatments to use and when to use
them, can be difficult due to small patient numbers and limited outcome data.
Furthermore, we are interested in specific outcomes for individual patients,
for example a 40-year old who may have undergone an intervention as a neonate. Unfortunately,
collecting robust data over a 40-year period is fraught with problems, not
least of all, over this long time period treatment options will enviably change.
Therefore, information from our current patients may not be useful as we would
like for neonates being operated on today.

Our
new approach is to use investigative data now being provided by imaging,
pressure monitoring, clinical observations and exercise to build representative
models of the heart and cardiovascular system. These models can be tested and
validated by using surgical/percutaneous interventions, or exercise/pharmacological
stimulations. The utility of these models is that we can begin to predict which
operation will provide the optimal result for any individual patient within in
a range of congenital heart disease such as Tetralogy of Fallot or single
ventricle; as well as acquired heart diseases such as hypertrophic
cardiomyopathy.

Over the last 7 years, we have used
cross-sectional imaging to assess how patients respond to treatments from a
physiological perspective, in particular before, during, and after percutaneous
device implantation (PPVI) and surgery. The research has had a direct impact on
patient selection for PPVI and surgery, and continues to improve the safety of
the technique. Our research has shown an increased success rate of PPVI
following the introduction of MRI cross-sectional imaging into the assessment
protocol.

In addition, we are using imaging techniques to
develop the next generation of PPVI devices and are now in the process of
developing imaging strategies for other forms of congenital heart disease,
aortic and mitral valve disease, and carcinoid disease.

There has always been a very sensitive issue
for parents when autopsy is required for foetuses, neonates, or infants. Our
preliminary data in this area suggests that for certain cases imaging may be
able to replace conventional autopsy. The data we have collected from over 400
cases may lead to a change UK policy for autopsy assessment in the future.

In 2009, we reported the first ever
whole-body imaging of a human at 9.4T (The Lancet 2009; 374:467) and developed
mechanisms whereby parents of children who are referred for forensic examination
(HM Coroners’
examinations in the UK) are able to volunteer their child to take part in the
research (The Lancet 2008; 372:715). This was previously not possible in the UK,
and may now provide a fundamental change to the way that parents can now be
approached. Future work in this area will focus on integrating post-mortem (PM)
MRI into clinical PM practice throughout the UK, and expand the use of
high-resolution MRI in this field.